PROJECT SUMMARY: FUNCTIONAL GENOMICS CORE (FGC) Functional genomics employs multiple technologies and genetic tools to study the complicated interactions between genotype and phenotype on a genome-wide scale. Genome-scale gain- and loss-of-function genetic screens are powerful tools for conducting such studies. The mission of the Functional Genomics Core (FGC; previously the CCSG Developing core shRNA and ORFeome Core) is to provide researchers at MD Anderson Cancer Center with cutting-edge technologies to study gene functions in cell-based assays. The FGC utilizes open reading frame (ORF), short hairpin RNA (shRNA), and guided RNA (gRNA) libraries to conduct genome- wide screens to identify oncogenes, tumor suppressors, metastasis regulators, drug resistance?conferring genes, and new therapeutic targets. Dr. Mien-Chie Hung, vice president for basic research and the chair of the Department of Molecular and Cellular Oncology, is the director of the FGC, and Dr. Dihua Yu is the co-director. During the current grant cycle MD Anderson provided $285,151 to purchase capital equipment and prior to 2012, provided funds to purchase FGC's libraries, including the pGIPZ shRNA library (human and mouse), human ORFeome Collaboration library, and Precision LentiORF library from GE Dharmacon and a human genome- wide pooled shRNA library from Cellecta. The FGC also has access to the Toronto KnockOut v3 human pooled gRNA library from Dr. Moffat's laboratory at the University of Toronto. Currently, the FGC provides 1) individual shRNA or ORF clones; 2) retro- and lenti-virus packaging; 3) custom shRNA or ORF libraries; 4) gene-knockout cell lines using CRISPR/Cas9 technology; and 5) project services to help researchers optimize screening assays, perform screens, and analyze data. The requested FGC grant Yr44 budget is $150,977/year; CCSG support would provide 33% of the budget. Since its inception, the FGC has provided services to 176 cancer center members in 64 departments at MD Anderson, representing all 16 CCSG programs. A total of 162 principal investigators have peer-reviewed support. During Yr42, all 80 users representing the 16 CCSG programs had received peer-reviewed funding. Most usage was by the Cancer Biology and Metastasis, Brain Cancer, and Breast Cancer CCSG programs, each of which was responsible for 12% of the total usage. During the grant period, the FGC facilitated 156 peer-reviewed publications, including 128 (82%) in journals with IF >5 and 59 (38%) in journals with IF >10, such as Nature, Cell, and Lancet Oncol. The FGC specific aims are: Aim 1: To provide functional genomics services to cancer center members; Aim 2: To perform genetic screens for basic/translational research and drug discovery; Aim 3: To implement new functional genomic technologies and augment existing services; Aim 4: To offer training and consultation to FGC users.